This is a phase 3, randomized, 2-arm, open-label, international trial evaluating alisertib compared with single-agent treatment, as selected by the investigator from the offered options of pralatrexate or gemcitabine or romidepsin, in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Note: romidepsin will not be used as a single-agent comparator in countries that do not permit its use at this time.

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:

Number of patients with overall response [ Time Frame: Change from screening period in response assessed at the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years ] [ Designated as safety issue: No ]

Number of patients with PFS [ Time Frame: Change from screening period in response assessed at the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years ] [ Designated as safety issue: No ]

Based on IRC assessment using a modified IWG (2007) criteria

Secondary Outcome Measures:

Number of patients with complete response + complete response unconfirmed [ Time Frame: Response assessed at the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years ] [ Designated as safety issue: No ]

Number of patients with overall survival [ Time Frame: Patients will be followed for survival for 2 years from date of last patient off study, or death, whichever occurs first. Contacts will be every 4 months. ] [ Designated as safety issue: No ]

Time to disease progression, duration of response, and time to response [ Time Frame: At the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years. ] [ Designated as safety issue: No ]

Number of adverse events, serious adverse events, assessments of clinical laboratory values and clinically important abnormalities, and vital sign measurements [ Time Frame: For each patient, from screening period to 30 days after last dose of study drug, approximately 1 year ] [ Designated as safety issue: Yes ]

Safety and tolerability of alisertib

Time to subsequent antineoplastic therapy [ Time Frame: From date of last study drug to date of subsequent antineoplastic therapy, if required; approximately 3 years ] [ Designated as safety issue: No ]

Changes in reported symptoms and Quality of Life (QOL) assessment per Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) for functioning and symptoms [ Time Frame: At screening period; Day 1 of each cycle; End of Treatment; Progression Free Survival follow-up. Duration approximately 3 years. ] [ Designated as safety issue: No ]

Patients randomized to receive alisertib will be administered an enteric-coated tablet formulation 5×10-mg twice daily orally for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle.

Active Comparator: Pralatrexate, or Romidepsin, or Gemcitabine

Pralatrexate,or Romidepsin,or Gemcitabine

Drug: Pralatrexate

Patients randomized to single-agent comparator will be assigned by the investigator to receive ONE of either Pralatrexate,or Romidepsin, or Gemcitabine.

Patients randomized to receive Pralatrexate will be administered the drug at 30mg/m2 as an intravenous (IV) push over 3 to 5 min once weekly for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles should be repeated every 7 weeks

Drug: Gemcitabine

Patients randomized to single-agent comparator will be assigned by the investigator to receive ONE of either Pralatrexate, or Romidepsin, or Gemcitabine.

Patients randomized to receive Gemcitabine will receive the drug intravenously at 1,000 mg/m2 over 30 minutes on Days 1, 8, and 15 of a 28-day cycle. Cycles should be repeated every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Romidepsin

Patients randomized to single-agent comparator will be assigned by the investigator to receive ONE of either Pralatrexate, or Romidepsin, or Gemcitabine.

Patients randomized to receive Romidepsin will be administered the drug intravenously at 14mg/m2 over a 4-hour period on Days 1,8,& 15 of a 28-cycle. Cycles should be repeated every 28 days.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Male or female patients age 18 or older

Patients with PTCL according to World Health Organization (WHO) criteria and have relapsed or are refractory to at least 1 prior systemic, cytoxic therapy for PTCL. Patients must have received conventional therapy as a prior therapy. Cutaneous-only disease is no permitted. Patients must have documented evidence of progressive disease.

Tumor biopsy available for central hematopathologic review

Measurable disease according to the IWG criteria

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Female patients who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 30 days after the last dose of study drug or agree to abstain from heterosexual intercourse.

Male patients who agree to practice effective barrier contraception through 6 months after the last dose of alisertib or agree to abstain from heterosexual intercourse

Suitable venous access

Voluntary written consent

Exclusion Criteria

Known central nervous system lymphoma

Systemic antineoplastic therapy, immunotherapy, investigational agent or radiation therapy within 4 weeks of first dose of study treatment or concomitant use during study

Prior administration of an Aurora A kinase-targeted agent, including alisertib; or all of the 3 comparator drugs (pralatrexate, or romidepsin or gemcitabine; or known hypersensitivity)

History of uncontrolled sleep apnea syndrome or other conditions that could result in excessive daytime sleepiness

The patient must have recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≤ 1 toxicity, to patients's baseline status (except alopecia), or deemed irreversible from the effects of prior cancer therapy

Major surgery, serious infection, or infection requiring systemic antibiotic therapy within 14 days prior to the first dose of study treatment

Female patients who are breastfeeding or pregnant

Coexistent second malignancy or history of prior solid organ malignancy within previous 3 years

Serious medical or psychiatric illness or laboratory abnormality that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01482962